The proposed plan for the K22 award is a one-year scholar phase, followed by a four-year faculty development phase. The scholar phase will provide for advanced postdoctoral training in the laboratory of Dr. Andrew Arnold at the University of Connecticut Health Center. This phase of mentored training will afford me the opportunity to focus my efforts on research and career development. During this phase, we will study the molecular mechanisms of hyperparathyroidism (HPT). Most cases of primary HPT are due to a solitary benign adenoma in one of the parathyroid glands. Molecular allelotyping and CGH have been used to identify areas in the genome where tumor suppressor genes involved in parathyroid tumorigenesis might be located. Interestingly, the frequent findings of LOH on chromosome 6 and 15 are commonly present in adenomas, but have not been noted in parathyroid carcinomas, suggesting that parathyroid adenomas and carcinomas may develop along separate pathways. This study will focus on deciphering the genetic changes that are particular to parathyroid adenomas through analysis of genetic losses and gene expression on chromosome 6 and 15. The hypothesis of this study is that the areas of LOH on chromosomes 6 and 15 are indicative of tumor suppressor genes, that when inactivated by mutation, contribute to benign parathyroid neoplasia. The research proposed for the faculty phase will study the genetic basis of non-syndromic maxillary/mandibular discrepancies, using many of the same techniques as the scholar phase project. The emergence of technologies to investigate complex human trait genetics has made it possible to begin to sort out the genetic basis of specific and quantifiable phenotypes. Relatively common skeletally based dentofacial dysmorphologies can result from discrepancies in the size, shape and/or position of the mandible and/or the maxilla. Such skeletal discrepancies can be classified into specific phenotype groups in order to construct genotype-phenotype maps for such dysmorphologies. The proposed research plan is to perform a genome wide screen to identify the quantitative trait loci (QTL) associated with the phenotypes being studied, and to narrow these regions to identify the candidate and/or novel genes involved in the craniofacial dysmorphologies investigated in this proposed project.